The primary objective of this research project is the isolation and structural elucidation of novel antimicrobial metabolites from marine organisms. The research will involve field collection of the marine organisms, bioassay-directed isolation of antimicrobial metabolites and the structural elucidation of these metabolites. Secondary objectives include the search for antifungal and certain cytotoxic metabolites from marine organisms, efforts to make active metabolites available for broader pharmacological screening and attempts to correlate the presence of antimicrobial metabolites with ecological parameters. The priorities for field collections are based on in situ screening, prior collecting experience and ecological clues. The marine organisms are collected by hand, primarily from tropical and subtropical locations. Extracts of the organisms are fractionated using antimicrobial assays to detect the active metabolites. We are primarily interested in the more polar active metabolites and are having to adapt analytical separation methods to deal with the purification of these metabolites. Pure compounds will be identified using all modern spectroscopic methods and the structures confirmed, when possible, by interconversion with known compounds. We anticipate that this research project will continue to generate antimicrobials with novel chemical structures. We will maintain a backlog of at least ten marine organisms that produce antimicrobial compounds by collecting at regular intervals. At present we have more than twenty active marine organisms in hand with four studies in progress. Using two collaborative screening programs, we will obtain the widest possible pharmacological screening for these antimicrobial metabolites.